Changes in ischemic tolerance and effects of ischemic preconditioning in middle-aged rat hearts

被引:98
作者
Tani, M
Suganuma, Y
Hasegawa, H
Shinmura, K
Hayashi, Y
Guo, XD
Nakamura, Y
机构
[1] Department of Geriatric Medicine, Keio University School of Medicine, Tokyo
[2] Department of Geriatric Medicine, Keio University School of Medicine, Shinjuku-Ku, Tokyo 160
关键词
aging; reperfusion; sarcoplasmic reticulum; creatine kinase; ischemia;
D O I
10.1161/01.CIR.95.11.2559
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Although both clinical and animal studies have shown that ischemic tolerance is reduced in the senescent myocardium, it has not been clarified when myocardium becomes more vulnerable to ischemia. Preconditioning protects the hearts of young adult animals of various species, but its effects are not identical in human studies. We investigated whether ischemic tolerance and the effect of preconditioning decreased in isolated hearts of middle-aged rats. Methods and Results The hearts of young adult rats (12 weeks old: group Y, n=44) and middle-aged rats (50 weeks old: group M, n=44) were subjected to global ischemia for 15, 20, or 25 minutes followed by reperfusion. Hearts were also subjected to preconditioning and then to 20 (group Y, n=22) or 15 (group M, n=22) minutes of ischemia followed by reperfusion. Left ventricular developed pressure (LVDP) was decreased by 40% to 60%, and the level of ATP was decreased by 60% to 70% in group M compared with group Y. Preconditioning increased LVDP (% LVDP, 40.5% to 72.4%) and levels of high-energy phosphates (ATP, 11.8 to 14.1; creatine phosphate, 17.0 to 23.1 mu mol/g dry wt) and reduced left ventricular end-diastolic pressure (LVEDP, 32.8 to 10.3 mm Hg), creatine kinase release (257 to 132 U/g dry wt), and ryanodine-sensitive sarcoplasmic reticulum Ca2+ release after ischemia in group Y. Preconditioning exerted opposite effects in group M (% LVDP, 45.9% to 15.8%; LVEDP, 21.0 to 28.5 mm Hg; ATP, 14.1 to 8.5 mu mol/g dry wt; and CK release, 176 to 332 U/g dry wt). Preconditioning was associated with increases in the incidence of reperfusion-induced Ventricular fibrillation (0% to 62.5%) and the rate of sarcoplasmic reticulum Ca2+ release in group M. Conclusions These results indicate that hearts became more vulnerable to ischemia with age and that the beneficial effects of preconditioning were reversed in middle-aged rat hearts.
引用
收藏
页码:2559 / 2566
页数:8
相关论文
共 48 条
[32]   DIMINISHED HEAT-SHOCK PROTEIN-70 MESSENGER-RNA INDUCTION IN AGED RAT HEARTS AFTER ISCHEMIA [J].
NITTA, Y ;
ABE, K ;
AOKI, M ;
OHNO, I ;
ISOYAMA, S .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 1994, 267 (05) :H1795-H1803
[33]   EFFECT OF AGE ON THE EXPRESSION OF ANTIOXIDANT ENZYMES IN MALE FISCHER-F344 RATS [J].
RAO, G ;
XIA, E ;
RICHARDSON, A .
MECHANISMS OF AGEING AND DEVELOPMENT, 1990, 53 (01) :49-60
[34]   EFFECTS OF ISCHEMIA ON THE ISOLATION AND FUNCTION OF CANINE CARDIAC SARCOPLASMIC-RETICULUM [J].
RAPUNDALO, ST ;
BRIGGS, FN ;
FEHER, JJ .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1986, 18 (08) :837-851
[35]   4 BRIEF PERIODS OF MYOCARDIAL-ISCHEMIA CAUSE NO CUMULATIVE ATP LOSS OR NECROSIS [J].
REIMER, KA ;
MURRY, CE ;
YAMASAWA, I ;
HILL, ML ;
JENNINGS, RB .
AMERICAN JOURNAL OF PHYSIOLOGY, 1986, 251 (06) :H1306-H1315
[36]   ISCHEMIC PRECONDITIONING REDUCES INFARCT SIZE IN SWINE MYOCARDIUM [J].
SCHOTT, RJ ;
ROHMANN, S ;
BRAUN, ER ;
SCHAPER, W .
CIRCULATION RESEARCH, 1990, 66 (04) :1133-1142
[37]   DIFFERENCES IN ISCHEMIA TOLERANCE BETWEEN HYPERTROPHIED HEARTS OF ADULT AND AGED SPONTANEOUSLY HYPERTENSIVE RATS [J].
SNOECKX, LHEH ;
VANDERVUSSE, GJ ;
COUMANS, WA ;
WILLEMSEN, PHM ;
RENEMAN, RS .
CARDIOVASCULAR RESEARCH, 1993, 27 (05) :874-881
[38]  
SOLLEVELD H A, 1986, Toxicologic Pathology, V14, P168, DOI 10.1177/019262338601400204
[39]   INTERMITTENT PERFUSION OF ISCHEMIC MYOCARDIUM - POSSIBLE MECHANISMS OF PROTECTIVE EFFECTS ON MECHANICAL FUNCTION IN ISOLATED RAT-HEART [J].
TANI, M ;
NEELY, JR .
CIRCULATION, 1990, 82 (02) :536-548
[40]   ROLE OF INTRACELLULAR NA+ IN CA-2+ OVERLOAD AND DEPRESSED RECOVERY OF VENTRICULAR-FUNCTION OF REPERFUSED ISCHEMIC RAT HEARTS - POSSIBLE INVOLVEMENT OF H+-NA+ AND NA+-CA2+ EXCHANGE [J].
TANI, M ;
NEELY, JR .
CIRCULATION RESEARCH, 1989, 65 (04) :1045-1056